Our hypothesis is that audiovestibular manifestation in relapsing polychondritis (RP) is caused by autoimmunity to specific epitope(s) on cyanogen bromide-11 (CB-11) peptide of type II collagen (CII). This may be tested by inducing ear lesions (auricular chondritis, eustachian tube chondritis, cochlear vasculitis) with monoclonal antibodies specific for these epitope(s). The long term objective of this proposal is to understand the basic pathogenic mechanisms of audiovestibular manifestation of relapsing polychondritis and a collagen autoimmunity in hearing loss. The specific approach of this proposal is to dissect the antibody repertoire, of mice which react with peptides obtained from CB-11 of CII and identify similar antibodies to type II collagen in human patients with relapsing polychondritis associated with hearing loss. 1. Develop a panel of monoclonal antibodies (Mab) specific for CB-11 peptide fragments of type II collagen obtained by cyanogen bromide (CBO digestion. 2. Identify the epitopic specificity of each Mab for small peptides obtained by isolation proteolytic fragments of CB-cleaved peptide (CB-11). 3. Induce collagen-induced ear disease with monoclonal antibodies with epitopes specificity of CB-11 peptide in mice. 4. Synthesize the chondriti inducing epitopic structure in CB-11 fragments and produce ear lesions in mice with these peptides. 5. Determine if antibodies from patients with relapsing polychondritis bind epitopes identified as important in the mouse model and to the synthetic ear lesions inducing peptide. Mice will be given monoclonal antibodies to induce ear disease. After finding ear disease inducing epitope, these peptides will also be made and ear disease will be induced by these synthetic peptides. Sera from RP with ear disease will be tested for the epitope specificity of these peptides and ear disease inducing epitope will be identified.